Chiara Ghiron

This literature study paper will present the possibility of a correlation between the Energy Meridians of Traditional Chinese Medicine (TCM), which can be traced back to the recently described Primo Vessels (formerly known as Bong-Han ducts), their composition and the ability of tumours to proliferate and metastasise. It is proposed that microvesicular bodies such as exosomes, known to be involved in cell-to-cell communication, immune response and tumour proliferation, could be moving across the body via the Primo Vascular System. The ubiquity of the Primo Vascular System and its penetration through the blood-brain barrier could also explain the ability of some peripheral tumours (e.g. breast tumour) to metastasise in the brain.

This literature study article will present the possibility of a correlation between the energy meridians of Traditional Chinese Medicine, which can be traced back to the recently described primo vessels (formerly known as Bong-Han ducts), their composition, and the ability of tumors to proliferate and metastasize. It is proposed that microvesicular bodies such as exosomes, known to be involved in cell-to-cell communication, immune response, and tumor proliferation, could be moving across the body via the primo vascular system. The ubiquity of the primo vascular system and its penetration through the bloodebrain barrier could also explain the ability of some peripheral tumors (e.g., breast tumor) to metastasize in the brain.

Two libraries of substituted benzimidazoles were designed using a 'scaffold-hopping' approach based on reported MDM2-p53 inhibitors. Substituents were chosen following library enumeration and docking into an MDM2 X-ray structure. Benzimidazole libraries were prepared using an efficient solution-phase approach and screened for inhibition of the MDM2-p53 and MDMX-p53 protein-protein interactions. Key examples showed inhibitory activity against both targets.

... Following the general procedure described, 650 mg of title compound were obtained as a light brown powder (52% yield). ... Suryakiran , N. ; Reddy , TS ; Latha , KA ; Prabhakar , P. ; Yadagiri , K. ; Venkateswarlu , Y. An expeditious synthesis of 3-amino 2H-pyrazoles promoted by ...

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α7 nicotinic acetylcholine receptor (nAChR) agonists are proposed as candidate agents for the adjunctive treatment of cognitive deficits associated with schizophrenia. Despite the pursuit of such an approach clinically, it is surprising that the preclinical profile of pro-cognitive agents in conjunction with antipsychotic drugs is currently unexplored. We determined if the memory-enhancing effects of the selective α7 nAChR agonist WYE-103914 were preserved in the presence of the atypical antipsychotic drug risperidone, and if the antipsychotic-like profile of risperidone was preserved in the presence of WYE-103914. Using the rat novel object recognition (NOR) paradigm, the maintenance of memory-enhancing activity of the α7 nAChR agonist WYE-103914 in the presence of risperidone was examined. Similarly, in the standard tests of antipsychotic-like activity, apomorphine-induced climbing (AIC) in mice and conditioned avoidance responding (CAR) in rats, the preservation of antipsychotic-like activity of risperidone was evaluated in the presence of WYE-103914. WYE-103914 exhibited memory-enhancing activity in rat NOR, and this effect of WYE-103914 was retained in the presence of risperidone. In AIC, the atypical antipsychotic profile of risperidone was not significantly altered by WYE-103914. In contrast, WYE-103914 moderately potentiated the efficacy profile of risperidone in CAR, an effect that did not appear to be convincingly linked to a pharmacokinetic interaction. These data underscore the value of a preclinical evaluation of the adjunctive profile of a memory-enhancing agent in combination with antipsychotics and provide further support to augmentation with α7 nAChR agonists to address the cognitive deficits associated with schizophrenia.

Alpha7 agonists were identified via GOLD (CCDC) docking in the putative agonist binding site of an alpha7 homology model and a series of aminoalkyl benzoimidazoles was synthesised to obtain potentially brain penetrant drugs. The array was prepared starting from the reaction of ortho-fluoronitrobenzenes with a selection of diamines, followed by reduction of the nitro group to obtain a series of monoalkylated phenylene diamines. N,N'-Carbonyldiimidazole (CDI) mediated acylation, followed by a parallel automated work-up procedure, afforded the monoacylated phenylenediamines which were cyclised under acidic conditions. Parallel work-up and purification afforded the array products in good yields and purities with a robust parallel methodology which will be useful for other libraries. Screening for alpha7 activity revealed compounds with agonist activity for the receptor.

Alpha-7 nicotinic acetylcholine receptor (α7 nAChR) agonists are promising therapeutic candidates for the treatment of cognitive impairment. We report a series of novel, potent small molecule agonists (4−18) of the α7 nAChR deriving from our continuing efforts in the areas of Alzheimer's ...

This is a conference presentation which I was invited to give in Chicago at the Natural Medicine Conference 2018 and is based on my recently published JAMS paper https://www.jams-kpi.com/article/S2005-2901(18)30075-X/fulltext.
Unfortunately the conference was cancelled due to dubious organisational practices, but I thought I'd share the presentation anyway.